医学
达沙替尼
伊马替尼
淋巴细胞白血病
甲磺酸伊马替尼
急性淋巴细胞白血病
随机对照试验
肿瘤科
内科学
随机化
代理终结点
儿科
费城染色体
临床试验
白血病
髓系白血病
染色体易位
化学
基因
生物化学
作者
Shuhong Shen,Xiaojuan Chen,Jiaoyang Cai,Jianhua Yu,Ju Gao,Shaoyan Hu,Xiaowen Zhai,Chaozhao Liang,Xiuli Ju,Hua Jiang,Runming Jin,Xuedong Wang,Ningling Wang,Xin Tian,Kaili Pan,Hui Jiang,Lirong Sun,Yongjun Fang,Chi Kong Li,Qun Hu,Minghua Yang,Yiping Zhu,Hui Zhang,Chunfu Li,Deqing Pei,Sima Jeha,Jun J. Yang,Cheng Cheng,Jingyan Tang,Xiaofan Zhu,Ching‐Hon Pui
出处
期刊:JAMA Oncology
[American Medical Association]
日期:2020-03-01
卷期号:6 (3): 358-358
被引量:155
标识
DOI:10.1001/jamaoncol.2019.5868
摘要
Importance
A randomized clinical trial is needed to determine whether the second-generation Abl–tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL). Objective
To determine whether dasatinib given at a daily dosage of 80 mg/m2is more effective than imatinib mesylate at a daily dosage of 300 mg/m2to improve event-free survival of children with Philadelphia chromosome–positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation. Design, Setting, and Participants
This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019. Interventions
Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. Main Outcomes and Measures
The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival. Results
Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%;P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%;P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups. Conclusions and Relevance
Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2per day yielded superior results in the treatment of Philadelphia chromosome–positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation. Trial Registration
Chinese Clinical Trial Registry:ChiCTR-IPR-14005706